Background Mindfulness is a trainable skill that may enhance resilience to suicidality among vulnerable groups such as young people. The current study examined whether mindfulness protects against suicidal desire in the face of heightened risk and adversity by increasing zest for life in a sample of university students. Methods In a prospective design, participants (N = 233) were assessed at two time points over eight weeks. Online surveys included the Mindful Attention and Awareness Scale, Zest for Life Scale, Interpersonal Needs Questionnaire, Kessler Psychological Distress Scale, and items assessing suicidal ideation and suicidal intent. Results Baseline mindfulness was associated with lower suicidal ideation and intent at follow-up. Moderated mediation analyses confirmed the effects of mindfulness on ideation and intent were mediated by zest for life and these indirect effects were stronger at higher versus lower levels of general (psychological distress) and suicide-specific (perceived burdensomeness and thwarted belongingness) risk. Limitations Single item assessments of suicidal desire. Conclusions Findings suggest that mindfulness protects against suicidal desire in conditions of heightened risk and adversity by enhancing one's orientation towards a life worth living. Theories of suicide should consider the dynamic interplay between risk and life-sustaining resilience, while clinicians treating suicidality could use mindfulness strategies to strengthen the desire to (re)engage with life, thereby complementing direct amelioration of suicide risk factors.